Limits...
Behavior training reverses asymmetry in hippocampal transcriptome of the cav3.2 knockout mice.

Chung NC, Huang YH, Chang CH, Liao JC, Yang CH, Chen CC, Liu IY - PLoS ONE (2015)

Bottom Line: We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout.Remarkably, the effect of Cav3.2 knockout was partially reversed by trace fear conditioning.To our knowledge, these results demonstrate for the first time the asymmetric effects of the Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.

ABSTRACT
Homozygous Cav3.2 knockout mice, which are defective in the pore-forming subunit of a low voltage activated T-type calcium channel, have been documented to show impaired maintenance of late-phase long-term potentiation (L-LTP) and defective retrieval of context-associated fear memory. To investigate the role of Cav3.2 in global gene expression, we performed a microarray transcriptome study on the hippocampi of the Cav3.2-/- mice and their wild-type littermates, either naïve (untrained) or trace fear conditioned. We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout. Between the naive Cav3.2-/- and the naive wild-type mice, 3522 differentially expressed genes (DEGs) were found in the left hippocampus, but only 4 DEGs were found in the right hippocampus. Remarkably, the effect of Cav3.2 knockout was partially reversed by trace fear conditioning. The number of DEGs in the left hippocampus was reduced to 6 in the Cav3.2 knockout mice after trace fear conditioning, compared with the wild-type naïve mice. To our knowledge, these results demonstrate for the first time the asymmetric effects of the Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

Show MeSH
Principal component analysis (PCA) is used to cluster the conditions with gene expression levels for (a) all genes, (b) 5282 genes that are differentially expressed in at least one of comparisons listed in Table 1.Each point corresponds to the gene expression pattern generated by an experimental group projected onto the two-dimensional principal component space.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4358833&req=5

pone.0118832.g004: Principal component analysis (PCA) is used to cluster the conditions with gene expression levels for (a) all genes, (b) 5282 genes that are differentially expressed in at least one of comparisons listed in Table 1.Each point corresponds to the gene expression pattern generated by an experimental group projected onto the two-dimensional principal component space.

Mentions: To summarize the effects of Cav3.2 gene knockout and TFC, on the left and right hippocampal transcriptome profiles, we analyzed the data by using Principal Component Analysis (PCA), and then plotted the first two Principal Components. The PCA plots allow visualizing the distance between different data sets in the dimensions that exhibit the major variations. We used all genes (Fig. 4a) and 5282 genes which were differentially expressed in at least one of comparisons listed in Table 1 (Fig. 4b) for each comparison group to plot the PCA. These two analyses gave almost identical results. Fig. 4 shows that KNL is farthest away from the rest of the data sets in the first principal component (PC1), indicating that the Cav3.2 gene knockout exhibited the largest effect on the transcriptome pattern. The rest of the data sets more or less clustered together, relative to KNL. By comparing KTL with KNL, we noted that after training (KTL), the trancriptome pattern of KNL returned to the same cluster as the WTL and WNL in PC1. This result confirmed that TFC largely reversed the effect of the Cav3.2 gene knockout. The second principal component (PC2) mainly separated between L and R samples in the wild-type (Fig. 4). Even though training reversed the effect of the Cav3.2 knockout in PC1, KTL transcriptome pattern did not return to the cluster of WTL and WNL in PC2. Rather, KTL was closer to the R samples in the PC2 dimension. This result indicates that behavioral training did not completely reverse the knockout effect, and the residual difference made the KTL pattern resemble the R samples.


Behavior training reverses asymmetry in hippocampal transcriptome of the cav3.2 knockout mice.

Chung NC, Huang YH, Chang CH, Liao JC, Yang CH, Chen CC, Liu IY - PLoS ONE (2015)

Principal component analysis (PCA) is used to cluster the conditions with gene expression levels for (a) all genes, (b) 5282 genes that are differentially expressed in at least one of comparisons listed in Table 1.Each point corresponds to the gene expression pattern generated by an experimental group projected onto the two-dimensional principal component space.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358833&req=5

pone.0118832.g004: Principal component analysis (PCA) is used to cluster the conditions with gene expression levels for (a) all genes, (b) 5282 genes that are differentially expressed in at least one of comparisons listed in Table 1.Each point corresponds to the gene expression pattern generated by an experimental group projected onto the two-dimensional principal component space.
Mentions: To summarize the effects of Cav3.2 gene knockout and TFC, on the left and right hippocampal transcriptome profiles, we analyzed the data by using Principal Component Analysis (PCA), and then plotted the first two Principal Components. The PCA plots allow visualizing the distance between different data sets in the dimensions that exhibit the major variations. We used all genes (Fig. 4a) and 5282 genes which were differentially expressed in at least one of comparisons listed in Table 1 (Fig. 4b) for each comparison group to plot the PCA. These two analyses gave almost identical results. Fig. 4 shows that KNL is farthest away from the rest of the data sets in the first principal component (PC1), indicating that the Cav3.2 gene knockout exhibited the largest effect on the transcriptome pattern. The rest of the data sets more or less clustered together, relative to KNL. By comparing KTL with KNL, we noted that after training (KTL), the trancriptome pattern of KNL returned to the same cluster as the WTL and WNL in PC1. This result confirmed that TFC largely reversed the effect of the Cav3.2 gene knockout. The second principal component (PC2) mainly separated between L and R samples in the wild-type (Fig. 4). Even though training reversed the effect of the Cav3.2 knockout in PC1, KTL transcriptome pattern did not return to the cluster of WTL and WNL in PC2. Rather, KTL was closer to the R samples in the PC2 dimension. This result indicates that behavioral training did not completely reverse the knockout effect, and the residual difference made the KTL pattern resemble the R samples.

Bottom Line: We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout.Remarkably, the effect of Cav3.2 knockout was partially reversed by trace fear conditioning.To our knowledge, these results demonstrate for the first time the asymmetric effects of the Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.

ABSTRACT
Homozygous Cav3.2 knockout mice, which are defective in the pore-forming subunit of a low voltage activated T-type calcium channel, have been documented to show impaired maintenance of late-phase long-term potentiation (L-LTP) and defective retrieval of context-associated fear memory. To investigate the role of Cav3.2 in global gene expression, we performed a microarray transcriptome study on the hippocampi of the Cav3.2-/- mice and their wild-type littermates, either naïve (untrained) or trace fear conditioned. We found a significant left-right asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout. Between the naive Cav3.2-/- and the naive wild-type mice, 3522 differentially expressed genes (DEGs) were found in the left hippocampus, but only 4 DEGs were found in the right hippocampus. Remarkably, the effect of Cav3.2 knockout was partially reversed by trace fear conditioning. The number of DEGs in the left hippocampus was reduced to 6 in the Cav3.2 knockout mice after trace fear conditioning, compared with the wild-type naïve mice. To our knowledge, these results demonstrate for the first time the asymmetric effects of the Cav3.2 and its partial reversal by behavior training on the hippocampal transcriptome.

Show MeSH